Targeting Metabolic Flexibility in Amyotrophic Lateral Sclerosis (ALS)
- Conditions
- Motor Neuron DiseaseAmyotrophic Lateral Sclerosis
- Interventions
- Registration Number
- NCT04788745
- Lead Sponsor
- The University of Queensland
- Brief Summary
MetFlex is an investigator led, open-label, single-arm, Phase 2a trial to determine the safety and tolerability of trimetazidine for the treatment of amyotrophic lateral sclerosis/motor neuron disease (ALS/MND).
- Detailed Description
The study will consist of a 4-week lead-in period to obtain a stable baseline measurement of clinical markers of disease and oxidative stress. After the lead-in phase, participants will receive trimetazidine for 12 weeks. Participants will visit the clinic at 6-week intervals, during which we will obtain a blood sample to measure the pharmacodynamic response. We will also collect information regarding the rate of disease progression (i.e. ALSFRS-R and SVC). At weeks 3 and 9 of treatment, participants will conduct a teleconference visit, during which we will collect data on ALSFRS-R. Adverse events will be collected and recorded throughout the entire trial duration. At the end of the on-treatment period, a close-out visit will occur after four weeks. The total study period per participant will be 20 weeks.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 21
-
Age between 18 and 75 years
-
Signed informed consent prior to the initiation of any study-specific procedures
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Familial or sporadic ALS/MND, defined as clinically possible, probable, or definite as per the El Escorial criteria
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Relative TRICALS risk score between -6.0 to -2.0 (75% of patients with ALS/MND)
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Metabolic index ≥110%, at the screening visit.
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The use of riluzole will be permitted during the study. Individuals taking riluzole must be on a stable dose for at least 30 days prior to the baseline visit, or stopped taking riluzole at least 30 days prior to the baseline visit.
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Ability to swallow tablets
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Able to lie with torso elevated at a 35° angle for 30 minutes without respiratory support
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Able to give informed consent (as judged by the investigator) and able to comply with all study visits and all study procedures
-
Females must not be able to become pregnant (e.g. post-menopausal, surgically sterile or using highly effective birth control methods) for the duration of the study. Highly effective methods of birth control are those with a failure rate of < 1% per year when employed consistently and correctly, e.g. Combined (oestrogen and progestogen containing) hormonal contraception associated with inhibition of ovulation:
- oral
- intravaginal
- transdermal
- Progestogen-only hormonal contraception associated with inhibition of ovulation:
- oral
- injectable
- implantable
- intrauterine device (IUD)
- intrauterine hormone-releasing system ( IUS)
- vasectomised partner
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Females of child-bearing potential must have a negative serum pregnancy test at screening and baseline and be non-lactating
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Unable to provide informed consent
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History of, or current diagnosis of diabetes or medical condition that impacts whole body energy expenditure (e.g. Hashimoto's, heart disease)
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Parkinson's disease or parkinsonism, tremor, restless-leg syndrome
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Safety Laboratory Criteria at screening related to significant kidney disease:
- Creatinine clearance < 50 mL / min (Cockcroft-Gault) based on Cystatin C
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Tracheostomy or non-invasive ventilation (NIV) use > 22 hours per day
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Inability to swallow tablets
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Contraindication therapy:
- Allergy for one of the product's active pharmaceutical ingredients (APIs) or excipients.
- Antihypertensive treatment [Trimetazidine may cause hypotension]
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Evidence of malignant disease
-
Significant neuromuscular disease other than ALS/MND
-
Ongoing disease that may cause neuropathy
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Pregnancy or breastfeeding
-
Females actively seeking to become pregnant who are not using an adequate form of contraceptive as detailed in the Inclusion criteria.
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Deprivation of freedom by administrative or court order
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SINGLE_GROUP
- Arm && Interventions
Group Intervention Description Experimental Trimetazidine Dihydrochloride Trimetazidine 35mg
- Primary Outcome Measures
Name Time Method Incidence of Treatment-Emergent Adverse Events; Safety and Tolerability 16 weeks The occurrence of adverse events, as assessed by Common Terminology Criteria for AEs Version 5, during the 12-week on-treatment period and 4-week wash-out period (16 weeks total).
Level of expression of oxidative stress markers in the plasma and/or serum of trial participants 16 weeks Expression of oxidative stress markers (malondialdehyde, 8-hydroxy-2'-deoxyguanosine, interleukin-6; assessed by liquid chromatography-mass spectrometry/mass-spectrometry or multiplexing) in the plasma and/or serum of trial participants throughout the treatment period (12-week) and at the end of the wash-out period (4 weeks)
- Secondary Outcome Measures
Name Time Method Level of expression of oxidative stress markers in the plasma and/or serum of trial participants to inform future clinical trials in ALS/MND 16 weeks Assessment of the expression of oxidative stress markers (malondialdehyde, 8-hydroxy-2'-deoxyguanosine, interleukin-6; assessed by liquid chromatography-mass spectrometry/mass-spectrometry or multiplexing) in the plasma and/or serum of trial participants throughout the treatment period (12-week) and at the end of the wash-out period (4 weeks) to determine suitability for incorporation into future trial design
Trial Locations
- Locations (3)
Royal Brisbane & Women's Hospital
🇦🇺Brisbane, Queensland, Australia
University Medical Centre Utrecht
🇳🇱Utrecht, Netherlands
King's College London
🇬🇧London, United Kingdom
Royal Brisbane & Women's Hospital🇦🇺Brisbane, Queensland, Australia